AJ12--Development/Production - Kidney GEC-Specific AAV Vector

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The following is a Sources Sought/Request for Information notice. This posted notice is not a Pre- Solicitation or Solicitation document. The government is not currently soliciting bids, quotes or proposals at this time; however, reserves the right to do so at a later date. The Harry S Truman Memorial Veterans Hospital, Columbia, MO 65201 has a brand name only requirement for Development/Production- Kidney GEC- Specific AAV Vector. Statement of Work (SOW) For GEC Targeted Adeno Associated Virus Vector Development Contract Description: Development and production of a kidney glomerular endothelial cell specific AAV vector for VA preclinical research. 1.0 Scope of Work: 1.1 This requirement is a VA ORD Merit funded project (#1I21RD001234-01) to develop a kidney glomerular endothelial cell specific viral vector. 1.2 The goal of the project is to build a homing peptide enabled vector platform capable of targeting the glomerular endothelium to treat kidney injury and disease and to enhance traditional pharmacologic approaches. 1.3 The work will modify the capsid of an endothelial specific, non immunogenic viral vector by incorporating a peptide that specifically targets kidney glomerular endothelial cells (GEC), with the objective of increasing specificity, reducing off target transduction, and overcoming known limitations in vector targeting to the kidney. 2.0 Background: 2.1 This requirement in response to RD-01-PILT: ISRM Pilot Project Award I21 was selected for funding by ORD; Merit funded project (1I21RD001234-01). 2.2 Despite aggressive management of blood pressure and glycemic control, the prevalence of kidney disease continues to rise, highlighting the need for adjunctive, individualized approaches that advance precision medicine. The project aims to build a homing peptide enabled vector platform targeting the glomerular endothelium to treat kidney injury and disease and to augment current therapeutic strategies. 2.3 Effective vector targeting of the kidney is impeded by the filtering function of the glomerulus and the risk of off target transduction, which may cause adverse effects. These challenges are compounded by the complex architecture of the kidney. Phage enabled peptide homing provides a powerful tool to refine tissue and cell specificity. Developing a targeted vector for GECs cells central to kidney disease development has strong potential to increase selectivity and minimize off target effects. 2.4 To address this need, the requirement leverages two technologies: (1) Biopanning with phage display to select peptides that specifically target kidney glomerular endothelial cells, and (2) capsid modification of an endothelial specific, non immunogenic vector to improve specificity and reduce off target transduction. 2.5 The services required will: 2.5.1 Validate a GEC targeting peptide and incorporate it into an endothelial specific adeno associated virus (AAV) capsid to control transduction specificity. 2.5.1.1Aim 1 refines phage display selection between murine and human renal versus extra renal endothelial cells to confirm GEC selectivity, followed by incorporation into the AAV capsid 2.5.2 Test the feasibility of the GEC specific AAV vector in culture studies (binding and internalization) and in vivo (biodistribution and transduction efficacy). 2.5.1.2 Aim 2 evaluates the targeting peptide modified AAV vector in murine kidney slices and in vivo biodistribution studies, followed by ex vivo immunofluorescent validation. The vector will also be tested in a murine model of endothelial glomerular filtration barrier injury. 2.6 This requirement will overcome current limitations in kidney specific vector targeting caused by the organ s complex cellular architecture and will create a clinically translatable cell specific vector platform designed to reduce off target effects. 3.0 Technical Requirements/Tasks: 3.1 Within one year of the start date of the funding award. The contractor shall independently perform all…

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